N,N-bis(methoxycarbonylmethyl)propargylamine

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N,N-bis(methoxycarbonylmethyl)propargylamine
• 英文别名: bis(methoxycarbonylmethyl)aminoprop-1-yne；methyl 2-[(2-methoxy-2-oxoethyl)-prop-2-ynylamino]acetate
• 化学式: C₉H₁₃NO₄
• 分子量: 199.207
• InChiKey: RZFBRZSBNSVQFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.73
• 重原子数：
  14.0
• 可旋转键数：
  5.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.84
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N,N-bis(methoxycarbonylmethyl)propargylamine 、 (S)-2-(5-bromo-pyridin-3-yloxymethyl)-azetidine-1-carboxylic acid tert-butyl ester 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 反应 1.0h， 以83%的产率得到5-[bis(methoxycarbonylmethyl)aminoprop-1-ynyl]-3-[(S)-1-(tertbutoxycarbonyl)-2-azetidinylmethoxy]pyridine
  参考文献：
  名称：

  Development of 99mTc radiolabeled A85380 derivatives targeting cerebral nicotinic acetylcholine receptor: Novel radiopharmaceutical ligand 99mTc-A-YN-IDA-C4

  摘要：

  Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that have been implicated in higher brain functions. To elucidate the functional mechanisms underlying nAChRs and contribute significantly to development of drugs targeting neurological and neuropsychiatric diseases, non-invasive nuclear medical imaging can be used for evaluation. In addition, technetium-99m (Tc-99m) is a versatile radionuclide used clinically as a tracer in single-photon emission computed tomography. Because A85380 is known as a potent alpha 4 beta 2-nAChR agonist, we prepared A85380 derivatives labeled with Tc-99m using a bifunctional chelate system. A computational scientific approach was used to design the probe efficiently. We used non-radioactive rhenium (Re) for a Tc-99m analog and found that one of the derivatives, Re-A-YN-IDA-C4, exhibited high binding affinity at alpha 4 beta 2-nAChR in both the docking simulation (-19.3 kcal/mol) and binding assay (Ki = 0.4 +/- 0.04 nM). Further, Tc-99m-A-YN-IDA-C4 was synthesized using microwaves, and its properties were examined. Consequently, we found that Tc-99m-A-YN-IDA-C4, with a structure optimized by using computational chemistry techniques, maintained affinity and selectivity for nAChR in vitro and possessed efficient characteristics as a nuclear medicine molecular imaging probe, demonstrated usefulness of computational scientific approach for molecular improvement strategy.

  DOI：

  10.1016/j.bmc.2019.07.053
• 作为产物：
  描述：

  dimethyl iminodiacetate hydrochloride 、 3-氯丙炔 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以99%的产率得到N,N-bis(methoxycarbonylmethyl)propargylamine
  参考文献：
  名称：

  Development of 99mTc radiolabeled A85380 derivatives targeting cerebral nicotinic acetylcholine receptor: Novel radiopharmaceutical ligand 99mTc-A-YN-IDA-C4

  摘要：

  Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that have been implicated in higher brain functions. To elucidate the functional mechanisms underlying nAChRs and contribute significantly to development of drugs targeting neurological and neuropsychiatric diseases, non-invasive nuclear medical imaging can be used for evaluation. In addition, technetium-99m (Tc-99m) is a versatile radionuclide used clinically as a tracer in single-photon emission computed tomography. Because A85380 is known as a potent alpha 4 beta 2-nAChR agonist, we prepared A85380 derivatives labeled with Tc-99m using a bifunctional chelate system. A computational scientific approach was used to design the probe efficiently. We used non-radioactive rhenium (Re) for a Tc-99m analog and found that one of the derivatives, Re-A-YN-IDA-C4, exhibited high binding affinity at alpha 4 beta 2-nAChR in both the docking simulation (-19.3 kcal/mol) and binding assay (Ki = 0.4 +/- 0.04 nM). Further, Tc-99m-A-YN-IDA-C4 was synthesized using microwaves, and its properties were examined. Consequently, we found that Tc-99m-A-YN-IDA-C4, with a structure optimized by using computational chemistry techniques, maintained affinity and selectivity for nAChR in vitro and possessed efficient characteristics as a nuclear medicine molecular imaging probe, demonstrated usefulness of computational scientific approach for molecular improvement strategy.

  DOI：

  10.1016/j.bmc.2019.07.053

文献信息

• Synthesis and Unprecedented Complexation Properties of β-Cyclodextrin-Based Ligand for Lanthanide Ions
  作者：Pier-Luc Champagne、Cécile Barbot、Ping Zhang、Xuekun Han、Issam Gaamoussi、Marie Hubert-Roux、Gabriel E. Bertolesi、Géraldine Gouhier、Chang-Chun Ling

  DOI：10.1021/acs.inorgchem.8b00937

  日期：2018.8.6

  Here, we report the synthesis and detailed studies on the coordination chemistry of a novel chemically modified polyaminocarboxylate (5) based on β-cyclodextrin (CD) scaffold for lanthanides. The target ligand is prepared in a highly efficient manner (seven total steps) from β-CD using the readily available iminodiacetic acid as a starting material. A propargyl group is attached to the iminodiacetate

  在这里，我们报告基于镧系元素的β-环糊精（CD）支架的新型化学修饰的聚氨基羧酸盐（5）的配位化学的合成和详细研究。使用容易获得的亚氨基二乙酸作为起始原料，以高效的方式（七个步骤）从β-CD制备目标配体。炔丙基通过N连接至亚氨基二乙酸酯-烷基化，并且所获得的衍生物经由铜（I）介导的1，3-偶极环加成而有效地缀合至β-CD支架。产生的1,2,3-三唑甲基残基有利地提供了有效的螯合基团，同时使金属配位中心远离β-CD的主要边缘，从而提供了所需的构象柔韧性。β-CD的两个相邻吡喃葡萄糖基单元中每个单元的官能团完成了镧系元素的独特创建的八价配位球，同时仍保留了一个用于动态水配位的位点。为了帮助研究CD配体5的配位化学，我们还设计了一个相关的麦芽糖苷配体6，该配体忠实地代表了配体5的一个亚金属结合部分。由于进行了HRMS和NMR研究，我们成功地阐明了合成配体的配位化学。配体5的八价配位球显示出对镧系元